p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions

Virchows Arch. 2010 Apr;456(4):395-401. doi: 10.1007/s00428-010-0900-1. Epub 2010 Mar 12.

Abstract

Two N-terminal isoforms characterize the p63 protein: the transactivating isoform TAp63 and the amino-terminal truncated isoform DeltaNp63. Two further N-terminal isoforms lacking exon 4 (d4TAp63 and DeltaNp73L) have been reported. Purpose of the study was to investigate the molecular expression of N-terminal p63 isoforms in benign and malignant breast tissues. Eighteen randomly selected cases of invasive breast carcinoma (IBC) of luminal type, two cases of in situ duct carcinoma (DCIS/DIN), and 20 specimens of normal and benign breast tissues were studied. All cases were immunostained for p63. Reverse polymerase chain reaction and nested PCR were performed to evaluate p63 N-terminal expression patterns. These isoforms whenever present were validated by sequencing. All cases of normal breast, benign lesions, and the two cases of DCIS/DIN expressed DeltaNp63 and TAp63 isoforms only. The two variants lacking exon 4 (DeltaNp73L and d4TAp63) were not found. All invasive carcinomas expressed the DeltaNp63 and TAp63 isoforms as well as the two short isoforms lacking exon 4 which were found in 11 (d4TAp63) and four (DeltaNp73L) cases. The present cases of luminal-type IBC showed p63 isoforms together with short variants lacking exon 4. These isoforms were not observed in non-neoplastic breast tissue. Presence of p63 in invasive breast carcinomas of luminal type, as seen at molecular level, suggests caution to include p63 as a marker of basal-like carcinomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast / metabolism
  • Breast Neoplasms / metabolism*
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Exons / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism

Substances

  • Biomarkers, Tumor
  • CKAP4 protein, human
  • Membrane Proteins
  • Protein Isoforms